This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This pilot project forms the first collaboration between between contraceptive researchers at ONPRC with the Kansas University Medical Center (KUMC), both recipients of U54 Contraceptive Center grants. Dr. Tash and colleagues recently designed and synthesized a new oral anti-spermatogenic agent, H2-gamedazole that shows reversible contraception without toxic side effects in male rats and rabbits. In order to move any new male contraceptive agent into human clinical trials, efficacy and safety must also be demonstrated in nonhuman primates. A single oral dose of H2-gamendazole at 1 mg/kg or 3 mg/kg will be administered to male rhesus monkeys to determine: (Aim 1) the temporal decline and recovery of sperm and spermatogenic staging in testes;and (Aim 2) the absolute bioavailability of oral H2-gamendazole. Weekly semen samples will be monitored for changes in sperm count and motility. Testis biopsies will be obtained before and after treatment for histology and staging of spermatogenesis, i.e. loss of spermatids in seminiferous tubules and their subsequent repopulation. To determine bioavailability and absorption, pharmacokinetic dynamics after both a single oral and intravenous dose of H2-gamendazole will be assessed at multiple time intervals post-administration by quantification of plasma H2-gamendazole levels. This project will provide the first proof-of-concept data in nonhuman primates for a highly promising, potent and reversible, non-hormonal anti-spermatogenic, oral contraceptive agent. Subsequent studies to establish contraceptive efficacy and safety studies in nonhuman primates will aid in ultimately moving H2-gamendazole toward human clinical trials as a novel male contraceptive agent. Animal trials began after generation of sufficient drug for systemic delivery in male monkeys.